This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Osteogenesis Imperfecta (OI) is a rare disorder of increased bone fragility that is most often due to abnormalities in type I collagen. Because of the rarity of this disorder and the pan-ethnicity of the disorder, there is no geographic clustering of individuals with OI and therefore there are no centers that have sufficient numbers of patients with OI to perform adequately powered studies alone. To date, large clinical research studies on the natural history or management of OI have not been performed. The majority of advances in medical care in the last few decades are informed by large, multicenter studies of natural history, drugs or devices for particular disorders. For rare disorders, the multicenter model is critical for obtaining enough information on enough individuals for a study to be valid. Toward this end, the OI Foundation has committed resources to the development of linked clinical research centers. There will be three centers in the first year of funding (Baylor College of Medicine, Houston, Texas;The Kennedy-Kreiger Institute, Baltimore, Maryland and Oregon Health Science University, Portland, Oregon) and a data collection and analysis center (University of South Florida College of Medicine, Tampa, Florida). It is expected that each center will enroll a minimum of 40 patients in the first 12 months of funding. We anticipate that additional centers will be added in subsequent years with around two dozen participant sites at year five of the LCRC initiative. The initial focus will be on performing a natural history study of OI and it is anticipated that from this, focused research questions will be developed to look at outcomes of medical and surgical management, including clinical trials of new therapeutic articles. A longitudinal multidisciplinary investigation of the natural history, morbidity, and mortality in people with osteogenesis imperfecta will improve treatment and outcome of this devastating disorder. The objective of this protocol is to conduct a longitudinal multidisciplinary investigation of the natural history, current therapeutic interventions, morbidity, and mortality in people with OI. The research questions are: a.In the longitudinal cohort, what is the prevalence of specific morbid indicators of disease severity, including fractures, pain, and functionality/mobility, as well as case-fatality associated with the various forms of OI? b.What is the relationship between various genotype and disease severity and progression? c.What is the safety and efficacy of currently used and new OI therapies?